We propose to develop within the Division of Oncology at the Fred Hutchinson Cancer Research Center a program devoted to the study and treatment of aplastic anemia. In vitro laboratory studies involving culture of hemopoietic cells will focus on the etiology of the disease; in vitro results will be correlated with clinical response to therapy. Monoclonal antibodies to T cell subsets will be used to dissect the role of lymphocytes in in vitro hemopoiesis. Results might help us in choosing the most suitable antibody for in vivo treatment of patients. Several treatment modalities will be evaluated in the setting of optimal supportive care which includes platelet transfusions, laminar air flow isolation, gut sterilization, bacteria-poor diet and, if necessary, granulocyte transfusions. Treatment with intensive supportive care alone will be compared to immunosuppressive therapy using either horse antihuman thymocyte globulin or monoclonal antibolies to T lymphocyte from HLA identical family members using a new conditioning regimen and a pos-grafting immunosuppresive therapy regimen involving cyclosporin A to reduce the rates of marrow graft rejection and graft-versus-host disease. A marrow transplant regimen for less well matched donors is proposed to obtain information on the importance of histcompatibility. Research on long term platelet support and management of infectious complications in this group of patients is proposed. Studies on immunologic reconstitution and long-term follow-up will be carried out. Data processing and biostatistic analyses will provide maximun utilization of information generated. Some of the principles derived from these studies will be applicable to the treatment of other diseases, e.g. thalassemia major, sickle cell disease and hematologic malignancy.